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Biomedical subjects

V J Wilson

Publications and source records attributed to V J Wilson.

At least 19 recordsLinked to original sources
PubMed2001

Commissural effects in the otolith system.

We examined whether otolith-activated second- and third-order vestibular nucleus neurons received commissural inhibition from the contralateral otolithic macula oriented in the same geometric plane. For this purpose we performed intracellular recording in vestibular nucleus neurons after stimulation of the ipsi- and contralateral utricular and saccular nerves. More than half (41/72) of the utricular-activated second-order vestibular nucleus neurons received commissural inhibition from the contralateral utricular nerve. The remaining neurons (31/72) showed no visible response to contralateral utricular nerve stimulation. About half (17/36) of utricular-activated third-order neurons also received commissural inhibition from the contralateral utricular nerve. Approximately 10% (7/67) of saccular-activated second-order vestibular neurons received polysynaptic commissural inhibition, whereas 16% (11/67) received commissural facilitation. The majority (49/67) of saccular second-order vestibular neurons, and almost all (22/23) third-order neurons, showed no visible response to stimulation of the contralateral saccular nerve. The present findings suggest that many utricular-activated vestibular nucleus neurons receive commissural inhibition, which may provide a mechanism for increasing the sensitivity of vestibular neurons to horizontal linear acceleration and lateral tilt of the head. Commissural inhibition in the saccular system was less prominent than in the utricular system.

Animals↗
PubMed1999

Cortical influences on the vestibular nuclei of the cat.

Our goal was to study potential substrates for cortical modulation of vestibular reflexes in the cat. In initial experiments, injections of wheat-germ-agglutinate-horseradish-peroxidase into Deiters' nucleus and the rostral descending nucleus revealed bilateral colonies of retrogradely filled neurons in cortical areas 6, 2, and 3a (about 60 cells per colony). In cats anesthetized with chloralose-urethane, we stimulated areas 2 and 3a with trains of pulses while recording from ipsilateral vestibular-nucleus neurons, which were characterized by their responses to sinusoidal tilts and tested for the presence of antidromic responses to stimulation of the upper cervical cord. A majority of the neurons was affected by cortical stimulation, showing either facilitation, inhibition, or a mixture of the two. Stimulation in area 2 was more effective than stimulation in area 3a. Despite the anatomic presence of direct cortico-vestibular projections, properties of facilitation and inhibition suggest that both were evoked by polysynaptic pathways. Cortical effects were broadly distributed to vestibular neurons without regard to responses of these neurons to sinusoidal tilts. There was no significant difference between effects on lateral and medial vestibulospinal tract neurons, but, as a group, vestibulospinal neurons were much more likely to be affected by cortical stimulation than neurons not antidromically activated from the C2 segment. We conclude that, by their influence on vestibulospinal neurons, neurons in cortical areas 2 and 3a should be able to modulate, in behaving animals, vestibular reflexes acting on the neck and limbs.

Animals↗
PubMed1999

The neural substrate of the vestibulocollic reflex. What needs to be learned.

The purpose of this review is to assess the role of short-latency pathways in the vestibulocollic reflex (VCR). First the current knowledge about the disynaptic and trisynaptic pathways linking semicircular canal and otolith afferents with cat neck motoneurons is summarized. We then discuss whether these pathways are sufficient or necessary to produce the responses observed in neck muscles by natural vestibular stimulation and conclude that they are neither. Finally, alternate pathways are considered, most likely involving reticulospinal fibers, which are an important part of the neural substrate of the VCR.

Animals↗
PubMed1998

Effects of hypophysectomy and growth hormone administration on the mRNA levels of collagen I, III and insulin-like growth factor-I in rat skeletal muscle.

The effect of short-term treatment of normal or hypophysectomized rats with biosynthetic growth hormone (GH) was studied in extensor digitorum longus and soleus muscles. In situ hybridization revealed that in normal rats, mRNA for collagen I, collagen III and insulin-like growth factor-I (IGF-I) are expressed by fibroblasts between the muscle fibre areas and that the specificity of this location was not altered by GH administration. Hypophysectomy appeared to cause a decrease in IGF-I and decreased collagen I and III gene expression (P < 0.001, P < 0.001, respectively). GH administration seemed to increase IGF-I mRNA levels in all the animals studied. Quantitative image analysis that GH administration to hypophysectomized rats caused an increase in collagen I gene expression after 2 days (P < 0.05) and an increase in collagen III gene expression after 4 days (P < 0.05). The results indicate that the fibroblast cells are an important target for the action of GH on skeletal muscle and that the fibroblasts respond to GH by increases in the expression of mRNA for collagen I and collagen III.

Animals↗
PubMed1997

Detection and cellular localization of heparin-binding epidermal growth factor-like growth factor mRNA and protein in human atherosclerotic tissue.

Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a member of the epidermal growth factor family which binds to and activates the epidermal growth factor (EGF) receptor. HB-EGF mRNA is expressed by monocytes and vascular smooth muscle cells (VSMC) in culture, and has been shown to be a potent VSMC mitogen in vitro. The aim of this study was to screen normal and human atherosclerotic arteries and SMC cultured from these arteries for expression of HB-EGF, and to determine its cellular localization in human lesions. Using the highly sensitive technique of reverse transcription polymerase chain reaction (RT-PCR), we screened biopsies taken from normal human vessel walls and atherosclerotic tissue, for expression of HB-EGF mRNA. Northern blotting and RT-PCR were employed to determine levels of HB-EGF gene expression in SMC, cultured from normal and atherosclerotic arteries. Cellular localization of mRNA and protein, within human atherosclerotic plaques, was assessed using in situ hybridization with 35S labelled riboprobes, and immunohistochemistry with polyclonal antibodies specific for human HB-EGF. HB-EGF mRNA was found to be expressed in human atherosclerotic lesions and in VSMC cultured from these lesions. Expression of HB-EGF could not be detected in quiescent aortic VSMC using Northern blotting, but was highly up-regulated in these cells after treatment with basic fibroblast growth factor (bFGF) for 24 h. Although HB-EGF mRNA was detected in all vascular tissue examined using RT-PCR, in situ hybridization and immunohistochemistry revealed expression of HB-EGF in small portions of diseased arteries only. Immunohistochemistry showed strong staining for macrophages in all areas of HB-EGF expression. No association of HB-EGF with SMC was observed in any of the specimens examined. In conclusion, HB-EGF, a potent mitogen for VSMC, is expressed by macrophages in human.

Arteries↗
PubMed1997

Excitatory connections between neurons of the central cervical nucleus and vestibular neurons in the cat.

The central cervical nucleus (CCN) of the cat receives input from upper cervical muscle afferents, particularly primary spindle afferents. Its axons cross in the spinal cord, and while in the contralateral restiform body give off collaterals to the vestibular nuclei. In order to study the connections between CCN axons and vestibular neurons, we stimulated the area of the CCN in decerebrate cats while recording intra- or extracellularly from neurons in the contralateral vestibular nuclei. CCN stimulation evoked excitatory postsynaptic potentials (EPSPs) or extracellularly recorded firing in the lateral, medial and descending vestibular nuclei. The latency of EPSPs (mean 1.6 ms) was on average 0.4 ms longer than the latency of antidromic spikes evoked in the CCN by stimulation of the contralateral vestibular nuclei (mean 1.2 ms), demonstrating that the excitation was typically monosynaptic. The results provide further evidence that the CCN is an important excitatory relay between upper cervical muscle afferents and neurons in the contralateral vestibular nuclei.

Animals↗
PubMed1996

Upregulation of IGF-I and collagen I mRNA in human atherosclerotic tissue is not accompanied by changes in type 1 IGF receptor or collagen III mRNA: an in situ hybridization study.

BACKGROUND: Immunoreactive insulin-like growth factor-I (IGF-I) has recently been localized to vascular smooth muscle cells in coronary atherectomy plaques, but it remains unclear whether these cells are the source of this growth factor. We therefore investigated the gene expression of this factor, and the expression of the genes for its receptor and two types of collagen known to be regulated by IGF-I, in vascular tissue samples from patients with atherosclerosis or restenosis. METHODS: Gene expression and localization were investigated by in situ hybridization, using 35S-labelled complementary RNA probes specific for IGF-I, its type a receptor, collagen I, and collagen III. The cellular composition of the tissue samples was determined by immunohistochemistry using antibodies specific for smooth muscle cells and macrophages. RESULTS: IGF-I and collagen I messenger RNAs were found in areas containing smooth muscle cells and macrophages, but collagen III and type 1 IGF receptor gene expression could not be detected in any tissue samples. CONCLUSION: IGF-I appears to be involved in the progression of the atherosclerotic plaque, even at an advanced stage, but preliminary data from two restenotic plaques indicate that it may not be involved in the later stages of restenosis.

Arteriosclerosis↗
PubMed1996

Tilt responses of neurons in the caudal descending nucleus of the decerebrate cat: influence of the caudal cerebellar vermis and of neck receptors.

1. In decerebrate cats with intact cerebellums, we studied the responses of neurons in the caudal areas of the vestibular nuclei to natural vestibular stimulation in vertical planes and to neck rotation. The activity of most neurons was recorded in the caudal half of the descending nucleus. 2. One goal of our experiments was to compare the dynamic and spatial properties of responses to sinusoidal vestibular stimulation with those seen in previous experiments in which the caudal cerebellar vermis, including the nodulus and uvula, was removed. This part of the cerebellum receives vestibular input and projects to the caudal areas of the vestibular nuclei, suggesting that it could influence responses to stimulation of the labyrinth. 3. As in our previous experiments, most neurons could be classified as receiving predominant input either from the otoliths or from one vertical semicircular canal. When mean gain and phase and response vector orientations were compared, there were no obvious differences between the behavior of neurons in the partially decerebellate preparation and the one with the cerebellum intact, demonstrating that in the decerebrate cat the nodulus and uvula have little or no influence on the processing of vertical vestibular input in this region of the vestibular nuclei. 4. Only 23 of 74 (31%) of neurons tested responded to neck rotation. This contrasts with the much larger fractions that respond to this stimulus in Deiters' nucleus and in the rostral descending nucleus. We also recorded from neurons near the vestibular nuclei, mainly in the external cuneate nucleus. All of them (9 of 9) responded to neck rotation. 5. Responses to neck rotation also differed in their dynamics from those found more rostrally in the vestibular nuclei. Dynamics of more rostral neurons resemble those of neck muscle spindles, as do those of external cuneate neurons. The dynamics of caudal vestibular neurons, on the other hand, have a steeper gain slope and more advanced phases than do those of neurons in the more rostral vestibular nuclei. This suggests the possibility of involvement of additional receptors in the production of these responses. 6. In the more rostral vestibular nuclei, responses to vestibular and neck rotation are most often antagonistic, so that head rotation results in little or no response. This is not the case in the caudal areas of the vestibular nuclei, where less than half the neurons tested displayed antagonistic behavior. Further experiments are required to put the neck projection to the caudal vestibular nuclei in a functional context.

Animals↗
PubMed1996

Vestibulospinal effects on neurons in different regions of the gray matter of the cat upper cervical cord.

1. Previous studies of vestibular effects on the upper cervical cord have concentrated on the lateral and medial vestibulospinal tracts and on the actions that they exert on neck motoneurons and other neurons in the ventral horn. It is known, however, that both the rostral and the caudal areas of the vestibular nuclei (VN) give rise to axons that are located in the dorsal and dorsolateral funiculi and that terminate in the dorsal horn. A primary goal of our experiments was to investigate the effect of VN stimulation on neurons dorsal to lamina VII. 2. In decerebrate cats with the caudal cerebellar vermis removed, we stimulated different areas of the VN with an array of electrode. The area of stimulation extended from the caudal tip of the descending nucleus to Deiters' nucleus, and was divided into rostral and caudal halves with the use of the descending nucleus as a reference. For control purposes some stimulating points were placed in the external cuneate nucleus and restiform body. 3. We tested the effects of VN stimulation on spontaneously firing neurons in the ipsilateral C2 and C3 segments. For purposes of classification the gray matter was divided into four zones corresponding approximately to laminae 1-IV, V-VI, VII, and VIII of Rexed. Overall, the activity of 39 of 84 neurons was influenced from one or more stimulating sites. For six cells there was some possibility of current spread to the external cuneate nucleus or to the underlying reticular formation. 4. VN-evoked effects could consist of facilitation, or, less often, inhibition. In the majority of facilitated neurons conditioning stimuli evoked a synchronized, short-latency, increase in firing probability. When evoked by single stimuli this facilitation was considered monosynaptic. Facilitation that was diffuse, or that was only evoked by two or more stimuli, presumably involved more complex pathways. The latency of inhibition could not be measured, but was short. 5. Stimulation of either the rostral or caudal VN had no effect on neurons in laminae I-IV. Electrodes placed rostrally had little effect on neurons in laminae V-VI, but influenced more than half the neurons in laminae VII-VIII. Conversely, electrodes placed caudally were most effective on cells in laminae V-VII, although they also influenced some neurons in lamina VIII. 6. Stimulation of the dorsal rami influenced most neurons in laminae V-VI, and about a quarter of the neurons in laminae VII-VIII. When tested, there was often convergence between vestibulospinal and peripheral inputs. 7. Our results provide physiological evidence that vestibulospinal fibers influence neurons not only in laminae VII and VIII, but also as far dorsally as lamina V. Fibers that influence neurons in laminae V and VI originate primarily in the caudal areas of the VN. As suggested previously on anatomic grounds, the projection to the dorsal laminae, which is predominantly facilitatory, often converges with afferent input and can therefore modulate its influence on spinal neurons.

Animals↗
PubMed1996

Responses of neurons of the cat central cervical nucleus to natural neck and vestibular stimulation.

1. The central cervical nucleus (CCN) is known to receive neck and vestibular input and to project to the contralateral cerebellum and vestibular nuclei. To investigate the processing of neck and vestibular input by cells in the CCN, we studied their responses to sinusoidal neck rotation and to whole-body tilt in vertical planes in decerebrate, paralyzed cats. CCN neurons were identified by antidromic stimulation with electrodes placed in or near the contralateral restiform body. 2. For every neuron, we first identified the preferred direction of neck rotation (response vector orientation), then studied the neuron's dynamics with rotations in a plane close to this direction at 0.05-1 Hz. 3. Responses of CCN neurons to neck rotation resembled those of previously studied neck spindle primary afferents in terms of their dynamics and nonlinear responses to stimuli of differing amplitudes. They also resembled the neck responses of Deiters' neurons studied in similar preparations. 4. The activity of two-thirds of CCN neurons also was modulated by natural vestibular stimulation. Orientation and dynamics of vestibular responses were characterized in the same way as neck responses. Labyrinthine input originated predominantly from the contralateral vertical canals, and there was no evidence of otolith input. Neck and vestibular inputs were always antagonistic, but the gain of the vestibular response was lower than that of the neck response at all frequencies studied. 5. The quantitative aspects of the interaction between neck and vestibular inputs can be expected to vary with the type of preparation and with stimulus parameters, and its functional significance remains to be investigated.

Afferent Pathways↗
PubMed1995

Growth hormone increases IGF-I, collagen I and collagen III gene expression in dwarf rat skeletal muscle.

The effect of short-term treatment with biosynthetic growth hormone (GH) of male dwarf rats was studied in EDL and soleus muscles. In situ hybridisation revealed that in the untreated dwarf rat collagen I, collagen III and insulin-like growth factor-I (IGF-I) mRNA is mainly expressed by fibroblasts between the muscle fibre areas. Quantitative image analysis showed that, 8 h after a single GH injection, the level of mRNA for all three genes increased compared to the untreated dwarf animal. IGF-I mRNA levels were similar in normals and untreated dwarf rats but significantly increased 8 h after a single GH injection in EDL (P < 0.01) and soleus (P < 0.001). In untreated dwarf rats, collagen I and III gene expression was significantly less than in normal animals (P < 0.001). Collagen III gene expression also increased significantly 8 h after a single GH injection, in both muscles (P < 0.01). Collagen I gene expression showed significant increases 8 and 24 h after GH treatment in EDL (P < 0.01), although the increases seen in soleus did not reach significance. The effects of multiple GH injections (one, two or four) did not appear to be additive. The results of the time course studies are consistent with an intermediary role for IGF-I in the production of collagen in muscle.

Animals↗
PubMed1995

Cervical primary afferent input to vestibulospinal neurons projecting to the cervical dorsal horn: an anterograde and retrograde tracing study in the cat.

Vestibulospinal neurons in the caudal half of the medial and descending vestibular nuclei terminate in the cervical spinal cord, not only in the ventral horn and intermediate zone but also in the dorsal horn. The purpose of the present study was to examine whether the areas containing these vestibulospinal neurons are reached by cervical primary afferents. In one group of experiments, wheat germ agglutinin-horseradish peroxidase conjugate and horseradish peroxidase were pressure injected into spinal ganglia C2-C8 and revealed anterogradely labeled fibers and boutons in the caudal part (caudal to the dorsal cochlear nucleus) of the ipsilateral medial and descending vestibular nuclei. This projection was verified in experiments in which wheat germ agglutinin-horseradish peroxidase conjugate was microiontophoretically injected into the caudal half of either the medial or the descending vestibular nuclei and revealed retrogradely labeled cells only in ipsilateral spinal ganglia C2-C7, with a maximum of cells in C3. In another group of experiments, after microiontophoretic injections of Phaseolus vulgaris leucoagglutinin or Biocytin into either the medial or the descending vestibular nuclei, anterogradely labeled fibers and boutons were present in the cervical spinal cord, mainly bilaterally in the dorsal horn (laminae I-VI) but also, to a lesser extent, in the ventral horn and intermediate zone. The existence of a loop that relays cervical primary afferent information to vestibulospinal neurons projecting to the cervical spinal cord, in particular the dorsal horn, may have implications for vestibular control over local information processing in the cervical dorsal horn.

Afferent Pathways↗
PubMed1995

Vertical vestibular input to and projections from the caudal parts of the vestibular nuclei of the decerebrate cat.

1. To investigate the type of vestibular signals that neurons in the caudal parts of the vestibular nuclei transmit to the cerebellum and spinal cord, we studied their responses to natural vestibular stimulation in vertical planes in decerebrate cats with the caudal cerebellum removed. Most neurons were in the caudal half of the descending vestibular nucleus, the remainder at corresponding levels of the medial nucleus or the medial-descending border. 2. Dynamics of the responses of spontaneously firing neurons were studied with sinusoidal tilts delivered at 0.05-1 Hz near the plane of body rotation that produced maximal modulation of the neuron's activity (response vector orientation). For most neurons the predominant vestibular input could be identified as coming from otolith organs (46%) or vertical semicircular canals (37%). Some neurons had otolith+canal convergence (9%) and others either had such converging input or some other form of central processing (8%). 3. Gain and phase of the responses of otolith neurons were comparable with values obtained in earlier studies on Deiters' nucleus and the rostral descending nucleus. Many canal neurons had a steeper gain slope and more advanced phase than observed previously for more rostral neurons. This may be due to more irregular afferent input to many neurons or to the absence of the vestibulocerebellum. 4. Response vector orientations of canal neurons were closely bunched near the planes of the ipsilateral vertical canals. The small number of contralaterally projecting vectors showed evidence of convergence between the two contralateral vertical canals. As is the case elsewhere in the vestibular nuclei, there was no evidence of convergence from bilateral vertical canals. Response vector orientations of otolith neurons were restricted to the roll quadrants; the majority pointed ipsilaterally. 5. Antidromic stimulation with an electrode in the restiform body or with several electrodes in the dorsal half of the white matter of the upper cervical cord was used to identify neurons projecting to the cerebellum and spinal cord, respectively. A substantial number of spontaneously firing neurons projected to the cerebellum, but there were few spontaneously active vestibulospinal neurons. The properties of the vestibular input to cerebellar-projecting neurons were the same as those of the population as a whole, but the effect of tilt on vestibulospinal neurons appeared weak or absent. 6. Many neurons were inhibited by stimulation of the restiform body. We suggest that this is mainly due to stimulation of the axons of vestibulocerebellar Purkinje cells. 7. Our results demonstrate a robust vertical vestibular input to the caudal parts of the vestibular nuclei.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1995

Effect of MLF transection on the vertical vestibulocollic reflex in decerebrate cats.

1. In the cat, motoneurons supplying biventer cervicis, complexus and rectus capitis posterior receive disynaptic input from the posterior semicircular canals and from the contralateral anterior canal via the medial vestibulospinal tract (MVST). Disynaptic excitation from the ipsilateral anterior canal reaches these motoneurons via the lateral vestibulospinal tract. 2. We hypothesized that if the MVST has a unique role in the production of the vertical vestibulocollic reflex (VCR) in these muscles then interruption of this tract by transection of the medial longitudinal fasciculus (MLF) would change the VCR responses. Specifically, response vector orientations would shift toward the plane of the ipsilateral anterior canal, and response gains would drop at high frequencies. 3. We lesioned the MLF bilaterally and observed no substantial effect on neck-muscle responses. Response vector orientations did not shift systematically toward a single plane, nor was there a consistent decrease in response gains at high frequencies. 4. As in the horizontal VCR, there is no unique contribution from MVST neurons; parallel pathways must play an important role in the vertical VCR.

Animals↗
PubMed1994

Changes in CCK mRNA in hippocampal neurones following fimbria fornix transection.

Preprocholecystokinin (CCK) mRNA expression was measured in a subset of hippocampal interneurones after transection of afferent septohippocampal fibres in the fimbria fornix. Two weeks after the lesions were made, CCK mRNA levels were significantly lower in these neurones on the side ipsilateral to the lesion compared with equivalent neurones on the unlesioned side. These findings suggest that axotomizing lesions can change gene expression in denervated target cells, and that CCK mRNA levels in hippocampal interneurones may be modulated by afferent septohippocampal input.

Afferent Pathways↗
PubMed1994

Response of commissural and other upper cervical ventral horn neurons to vestibular stimuli in vertical planes.

1. To study their contribution to the vestibulocollic reflex, we have studied, in decerebrate paralyzed cats, the effect of sinusoidal vestibular stimulation in multiple vertical planes on the spontaneous activity of neurons in the C3 ventral horn. Antidromic microstimulation was used to identify 17/42 neurons as commissural; 10 of these were confirmed to have a projection to the contralateral ventral horn. 2. Dynamics of the responses of spontaneously firing neurons were studied with 0.05-1 Hz sinusoidal stimuli delivered near the plane of rotation that produced maximal modulation of neuron activity (response vector orientation). On the basis of their responses, we classified 38 neurons as receiving otolith, semicircular canal, or otolith + canal input. All three response types were found among commissure and nonantidromic neurons. 3. Two-thirds of neuron response vector orientations pointed contralaterally. They were either near the anterior or posterior canal planes or in the roll quadrant. In the case of neurons with input from canals, the latter indicates convergence from the vertical canals on the same side. There were almost no vectors in the pitch quadrants. The distribution of response vector orientations resembles that seen in the vestibular nuclei and pontomedullary reticular formation, suggesting that commissural neurons may not make a new contribution to spatial processing in the vertical vestibulocollic reflex. 4. It is presumed that commissural neurons are premotor. If so, some have the properties to be in the pathway between the contralateral utricle and neck motoneurons. More generally, their actions could modify the effectiveness of vestibulospinal and reticulospinal fibers that have similar spatial properties and make synapses with neck motoneurons.

4-Aminopyridine↗
PubMed1993

Horizontal canal input to upper cervical commissural neurons.

We studied in decerebrate, paralyzed cats, the effect of sinusoidal yaw rotation on upper cervical commissural neurons. The activity of some neurons was modulated by this stimulus, and they were classified as receiving input from the horizontal semicircular canal. The responses, which were mainly type II, were well correlated with the velocity of the stimulus. These commissural neurons, some of them propriospinal, transmit horizontal canal signals to the contralateral ventral horn, presumably to motoneurons, as well as to more caudal levels of the spinal cord.

Animals↗